Gnesutta N, Qu J, Minden A
Department of Biological Sciences, Columbia University, New York, New York 10027, USA.
J Biol Chem. 2001 Apr 27;276(17):14414-9. doi: 10.1074/jbc.M011046200. Epub 2001 Jan 24.
The serine/threonine kinase PAK4 was identified first as an effector molecule for the Rho GTPase Cdc42. PAK4 differs from other members of the PAK family both in sequence and function. Previously we have shown that an important function of this kinase is to mediate the induction of filopodia in response to activated Cdc42. Studies with a constitutively active PAK4 mutant have shown that it also has a role in promoting anchorage-independent growth, an important hallmark of oncogenic transformation. Here we show that another function of PAK4 is to protect cells against apoptotic cell death. Expression of wild-type or constitutively active PAK4 delays the onset of apoptosis in response to tumor necrosis factor alpha stimulation, UV irradiation, and serum starvation. Consistent with an antiapoptotic function, expression of PAK4 leads to an increase in phosphorylation of the proapoptotic protein Bad and an inhibition of caspase activation.
丝氨酸/苏氨酸激酶PAK4最初被鉴定为Rho GTP酶Cdc42的效应分子。PAK4在序列和功能上均与PAK家族的其他成员不同。此前我们已经表明，该激酶的一个重要功能是介导丝状伪足的形成以响应激活的Cdc42。对组成型活性PAK4突变体的研究表明，它在促进不依赖贴壁生长方面也发挥作用，这是致癌转化的一个重要标志。在此我们表明，PAK4的另一个功能是保护细胞免受凋亡性细胞死亡。野生型或组成型活性PAK4的表达可延迟肿瘤坏死因子α刺激、紫外线照射和血清饥饿诱导的凋亡发生。与抗凋亡功能一致，PAK4的表达导致促凋亡蛋白Bad的磷酸化增加并抑制半胱天冬酶激活。
